Objective:To explore the effect of tyrosine kinase inhibitor (TKI) dose reduction regimen in patients with chronic-phase chronic myeloid leukemia (CML) and its prognostic impact.Methods:A retrospective cohort study was conducted. The clinical data of patients with chronic-phase CML treated with reduced-dose TKI in the First Affiliated Hospital of Soochow University between January 2018 and December 2022 were collected. Patients were divided into groups based on Sokal score, European Treatment and Outcome Study long-term survival (ELTS) score, TKI drug classification and dose reduction, and treatment phase. The overall survival (OS), the cumulative incidence of major molecular response (MMR), the cumulative molecular recurrence rate and event-free survival (EFS) among patients in different strata were compared. Kaplan-Meier method was used for survival analysis.Results:Among 154 patients with chronic-phase CML, the median duration [ M ( IQR)] of reduced-dose TKI therapy was 35.4 months (34.9 months); Sokal score high-risk and low-/intermediate-risk groups comprised 20 cases (12.99%) and 134 cases (87.01%), respectively; ELTS score high-risk and low-/intermediate-risk groups comprised 14 cases (9.09%) and 140 cases (90.91%), respectively. Among 154 patients, 83 cases (53.90%) received imatinib therapy, while 71 cases (46.10%) received second-generation TKI; 138 patients (89.61%) maintained stable TKI dosing at the first dose level, and 16 patients (10.39%) maintained it at the second dose level. The induction therapy group comprised 33 patients (21.43%), while the maintenance therapy group included 121 patients (78.57%). The 3-year OS rate of all 154 patients was 90.6%. Patients in the Sokal score high-risk group demonstrated a lower 3-year OS rate compared to those in the low-/intermediate-risk group (64.1% vs. 96.7%) ( P < 0.001); patients in the ELTS score high-risk group had a lower 3-year OS rate compared to those in the low-/intermediate-risk group (62.9% vs. 95.8%) ( P = 0.002). There was no statistically significant difference in the 3-year OS rate of patients receiving the first dose level and those receiving the second dose level (90.6% vs. 90.0%, P = 0.478); there was no statistically significant difference in the 3-year OS rate of the induction therapy group and the maintenance therapy group (88.9% vs. 91.4%, P = 0.868). Among the 33 patients in the induction therapy group, all received the first dose level. After treatment, 28 achieved MMR, and 2 achieved molecular response 4.0 (MR4.0). The cumulative 1-year MMR rate of all patients in reduction therapy group was 95.8%, with a median time to MMR of 8.4 months; patients in the high-risk Sokal score group had a 1-year cumulative MMR rate of 50.0%, which was lower than that of the low-/intermediate-risk group (95.3%) ( P = 0.014); the median time to MMR was 14.7 months and 7.8 months, respectively. The cumulative 1-year MMR rate of patients treated with first-generation TKI was lower than that in those treated with second-generation TKI (65.0% vs. 100.0%, P = 0.034), and the median time to MMR of patients treated with first-generation TKI was longer than that those treated with second-generation TKI (9.1 months vs. 6.9 months). Among the 149 patients who achieved MMR, 5 experienced molecular relapse, resulting in a 3-year cumulative molecular relapse rate of 8.3%. In the Sokal score low-/intermediate-risk group, the 3-year cumulative molecular relapse rate (1.5% vs. 39.8%, P < 0.001), EFS rate (92.3% vs. 57.1%, P < 0.001), and OS rate (100.0% vs. 62.8%, P < 0.001) were better than those in the Sokal score high-risk group. The 3-year cumulative molecular relapse rate and 3-year EFS rate in patients receiving first dose level therapy were better than those in patients receiving second dose level therapy, and the differences were statistically significant (all P < 0.001). Conclusions:Patients with chronic-phase CML can still obtain good outcomes when receiving dose-reduced TKI, while the prognosis of patients in high-risk group is relatively poor. The choice of TKI and the dosage reduction should be individualized based on patients' characteristics.

Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR)signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q)molecular features in lower-grade gliomas (LGG),and to construct and verify the predictive model based on magnetic resonance imaging (MRI)tumor features and T2-FLAIR signal suppression rate.Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2～3)in our medical center from 2017 to 2021 were collected and retrospectively analyzed.According to the results of postoperative molecular pathology,they were divided into 1 p/19q-codeleted (1 p/19q-Codel)and 1 p/19q-noncodeleted (1 p/19q-Noncodel)groups.MRI tumor features were blindly assessed by 2 neuroradiologists.Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate.The differences of clinical features,MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups.Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram.Receiver operating characteristic (ROC)curve,calibration curve and Hosmer-Lemeshow test were applied to assess the model performance,and the model was internally validated by bootstrap method.Results A total of 146 supratentorial LGG patients were enrolled,including 68 being assigned into the 1 p/19q-Codel group and 78 into the 1 p/19q-Noncodel group.The T2-FLAIR signal suppression rate was 0.43 (0.28,0.62)in the 1 p/19q-Noncodel group,which was significantly higher than that in the 1 p/19q-Codel group[0.29 (0.24,0.35),P<0.001].Multivariate logistic regression analysis showed that T2-FLAIR signal suppression rate>0.374 (P<0.001),cortex infiltration (P=0.001) and calcification (P=0.004) were independent predictors for 1 p/19q status.The AUC value of T2-FLAIR signal suppression rate>0.374 in predicting 1 p/19q-Noncodel was 0.720,the sensitivity was 60.26％ and the specificity was 83.82％.DeLong test indicated that T2-FLAIR signal suppression rate>0.374 was more effective than T2-FLAIR mismatch sign in predicting 1 p/19q molecular features (P<0.001).ROC curve analysis suggested that the predictive model established by T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification had good performance,with an AUC value of 0.808,and the AUC value verified internally by bootstrap method was 0.807.At the same time,the calibration and goodness of fit of the model were good.Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1 p/19q-Noncodel LGG.The predictive model with T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification can effectively predict 1 p/19q molecular features.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

OBJECTIVE To establish the quality standard of Lixieling tablets. METHODS Thin layer chromatography was used to identify Bistortae Rhizoma, Andrographis Herba and Sophorae Flavescentis Radix in Lixieling tablets. The components of andrographolium and matrine were determined by HPLC. RESULTS The thin layer spots of Bistortae Rhizoma, Andrographis Herba and Sophorae Flavescentis Radix were clear, with good separation effect and repeatability. The linear relationship between andrographolide, neoandrographolide, 14-deoxygenated andrographolide, dehydrated andrographolide, sophorine, oxymatrine, sophorine and oxysophorine and their respective concentration ranges was good. The RSDs of instrument precision, repeatability, stability and recovery all met the requirements. CONCLUSION The method is simple and reproducible, and can be used for the quality control of Lixieling tablets.

Extracellular matrix (ECM) components confer biomechanical properties, maintain cell phenotype and mediate tissue homeostasis. ECM remodeling is complex and plays a key role in both physiological and pathological processes. Matrix metalloproteinases (MMPs) are a group of enzymes responsible for ECM degradation and have been accepted as a key regulator in ECM remodeling. In this mini-review, we summarize MMPs categories, functions and the targeted substrates. We then discuss current understanding of the role of MMPs-mediated events, including inflammation reaction, angiogenesis, cellular activities, etc., in ECM remodeling in the context of regenerative medicine.

Objective:To study the effects of electron beam irradiation and 60Co irradiation on the composition changes of four alkaloids in Sophorae Flavescentis Radix, intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets. Methods:Sophorae Flavescentis Radix, intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets were irradiated at different doses of 0, 1.5, 3, 5, 7, 10, 20, 30, 40 kGy by electron beam irradiation and 60Co irradiation. The contents of oxymatrine, oxysophocarpine, matrine and sophocarpine were determined by HPLC, and the changes of the components before and after irradiation were compared. Results:Oxymatrine, oxysophocarpine, matrine and sophocarpine were among 0.046 9-0.937 4 μg, 0.020 5-0.410 4 μg, 0.098 9-1.977 9 μg, 0.048 7-0.973 1 μg, respectively. The linear relationship was good. The average recovery rates were 98.1%, 100.1%, 100.5%, 96.6%, respectively, and the RSDs were 1.69%, 2.03%, 3.14% and 1.10%, respectively. Electron beam irradiation and 60Co irradiation had no statistical significance on the changes of oxymatrine, oxysophocarpine, matrine and sophocarpine in Sophora flavescens, but had statistical significance in the contents of intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets. Conclusion:The established method for the determination of matrine is accurate, reproducible, simple and practical, and can be used for the quality control of Lixieling Tablets. Irradiation has no significant effect on the content of Sophorae Flavescentis Radix, while high dose irradiation has significant effect on the intermediates and finished products of Sophorae Flavescentis Radix, which can provide a basis for quality control and sterilization irradiation of enterprises.

Abstract: To investigate the changes of cerebral blood flow(CBF) in patients with type 2 diabetes mellitus(T2 DM) and its correlation with cognitive function and olfactory impairment. Methods: Cognitive function assessment and smell identification test were performed on 83 patients with T2 DM and 62 healthy controls(HC). Three-dimensional pseudo-continuous arterial spin labeling(3 D-pcASL) head images were collected from the two groups. CBF values of the cerebral cortex were compared between the patients and HC after the postprocessing. Correlations between the CBF values and cognitive function assessment and between the CBF values and smell identification test scores were analyzed as well. Results: Compared to the HC, Chinese smell identification test(CSIT), montreal cognitive assessment(MoCA), digit span test(DST), verbal fluency test(VFT) scores were lower in T2 DM patients(P<0.05).The CBF of the bilateral middle frontal gyrus in T2 DM patients was higher than that in HC group(P<0.001). The CBF of the bilateral gyrus rectus and olfactory cortex in T2 DM patients was lower than that in HC group(P<0.001). Conclusion The cognitive and olfactory function of patients with T2 DM decreased. Patients with T2 DM have abnormal perfusion in the bilateral middle frontal gyrus, gyrus rectus and olfactory cortex, revealing that CBF changes in these brain regions may be one of the causes for cognitive impairment and olfactory dysfunction in T2 DM.

Objective: To investigate the feasibility of using a carbon dioxide(CO2) laser in the treatment of facial papilloma in children and to evaluate its curative effect and prognosis. Methods : A case of pediatric facial papilloma treated with a CO2 laser was reported, and the effects of this disease and CO2 laser treatment were reviewed and analyzed in combination with the literature. Results: Under general anesthesia, the lesion tissue of the left lip was excised for pathological biopsy, and the diagnosis was maxillofacial papilloma. The lesions were surgically ablated in stages with a CO2 laser, and erythromycin ointment was applied to the surgical incision after surgery. A total of three rounds of CO2 laser treatment were performed for 3 treatment courses. The child had no complications during or after the operation, the facial appearance was significantly improved, and there was no sign of recurrence during the 6-month follow-up. A literature review showed that CO2 lasers have been widely used in the excision of various surface lesions. In clinical practice, continuous CO2 laser with power of 10-50 W and wavelength of 10.6 μm is used to treat superficial tissue lesions, which can achieve accurate vaporization resection of diseased tissue, less bleeding and a good prognosis. Conclusion CO2 laser was accurate and minimally invasive for the removal of facial papilloma in children.

The development and implement of microbial chassis cells can provide excellent cell factories for diverse industrial applications, which help achieve the goal of environmental protection and sustainable bioeconomy. The synthetic biology strategy of Design-Build-Test-Learn (DBTL) plays a crucial role on rational and/or semi-rational construction or modification of chassis cells to achieve the goals of "Building to Understand" and "Building for Applications". In this review, we briefly comment on the technical development of the DBTL cycle and the research progress of a few model microorganisms. We mainly focuse on non-model bacterial cell factories with potential industrial applications, which possess unique physiological and biochemical characteristics, capabilities of utilizing one-carbon compounds or of producing platform compounds efficiently. We also propose strategies for the efficient and effective construction and application of synthetic microbial cell factories securely in the synthetic biology era, which are to discover and integrate the advantages of model and non-model industrial microorganisms, to develop and deploy intelligent automated equipment for cost-effective high-throughput screening and characterization of chassis cells as well as big-data platforms for storing, retrieving, analyzing, simulating, integrating, and visualizing omics datasets at both molecular and phenotypic levels, so that we can build both high-quality digital cell models and optimized chassis cells to guide the rational design and construction of microbial cell factories for diverse industrial applications.
Bacteria/genetics* ; Metabolic Engineering ; Synthetic Biology

Objective: To investigate the effect of pituitrin-water separation on hemoglobin and ovarian function in laparoscopic ovarian chocolate cyst removal. Methods: From February 2018 to February 2019, 82 patients with ovarian chocolate cyst removed by laparoscopy were selected from the Second Affiliated Hospital of Wenzhou Medical University.They were randomly divided into observation group and control group according to the digital table, with 41 cases in each group.The control group underwent traditional laparoscopic tear-and-tear ovarian cyst removal, while the observation group underwent pituitrin-water separation.The changes of perioperative indicators, the decrease of hemoglobin (Hb) before and after operation, the positive rate of normal ovarian tissue on cyst wall and the number of normal follicles attached to cyst wall, the changes of serum hormone levels before and after operation were compared between the two groups. Results: The amount of bleeding during operation in the observation group [(58.97±8.74)mL] was less than that in the control group [(118.93±24.21)mL], and the operation time in the observation group[(57.46±8.27)min] was shorter than that in the control group [(87.38±10.19)min] , the differences were ststistically significant between the two group(t=14.916, 14.598, all P<0.05). There was no statistically significant difference in the time of anal exhaust between the two groups (P>0.05). The decrease of Hb in the observation group [(0.71±0.16)g/L] was lower than that in the control group [(1.27±0.35)g/L] (t=9.318, P<0.05). The positive rate of normal ovarian tissue on cyst wall in the observation group (21.95%) was lower than that in the control group (56.10%), the number of normal follicles attached to the cyst wall in the observation group (2.65±0.49) was less than that in the control group (4.86±1.24) , the differences were ststistically significant between the two group(χ²=10.045, t=10.613, all P<0.05). The serum level of E₂ [(398.21±17.84)pmol/L] in the observation group was higher than that in the control group [(367.83±15.21)pmol/L], while FSH [(6.72±0.28)mIU/mL] and LH [(5.23±0.38)mIU/mL] levels in the observation group were lower than those in the control group [(7.19±0.35)mIU/mL and (5.69±0.31)mIU/mL], the differences were ststistically significant between the two group (t=8.298, 6.714, 6.006, all P<0.05). Conclusion The method of pituitrin-water separation is effective in laparoscopic ovarian chocolate cyst removal, which can reduce the injury during operation, has little effect on hemoglobin and improve the ovarian reserve function of patients.